An X-ray and natural bond orbital (NBO)‎ structural study of a-tocopheryl and 2, 2, 5, 7, 8 pentamethylchroman-6-yl succinates

Abstract EN

α-Tocopheryl succinate (α-TOS) is a very promising anticancer agent; however, the mechanism of its action and the role of the succinic moiety in biological activity still remains unclear.

This paper, presents the first determination of the X-ray structure of α-TOS and 2,2,5,7,8-pentamethylchroman-6-yl succinate (PMCS).

The X-ray data indicated high out of planarity deformation of the aryl ring in the chroman-6-ol system.

α-TOS and PMCS differed in angle θ value (28.4° vs.

21.5°, respectively) and in their heterocyclic ring conformations: 2-endo-3-exo in PMCS, and 2-endo-3-exo and 2-exo-3-endo in α-TOS.

Due to their strong intermolecular hydrogen bonds, both succinates form cyclically repeated dimeric structures in well assembled crystal supramolecular structures.

A population analysis of α-tocopherol (α-TOC), 2,2,5,7,8-pentamethylchroman-6-ol (PMC) and their acyl derivatives was performed at B3LYP/6-31G(d,p)/CPCM level of theory using a natural bond orbital (NBO) analysis within the Gaussian 09 program package.

For all compounds, relaxed scans were performed along torsion angle γ, and for low-energy conformers the Fukui functions were calculated: electron donor (ƒ−(r)), electron acceptor (ƒ+(r)), free radical (ƒo(r)) and dual descriptor (ƒ2(r)).

In general, the differences observed between α-TOC and its acyl derivative structures result from the non-bonding lone pair of the phenolic oxygen and its interaction with aromatic system π electrons.